Nucleosides comprise a D-ribose or 2-deoxy-D- ribose sugar unit, chemically bonded to a purine or pyrimidine base selected from adenine, cytosine, guanine, thymine and uracil, via a nuclear nitrogen atom of the base. Since they are units of nucleic acids found naturally in living cells, it has been speculated previously that nucleosides and nucleotides and their related analogs might have potential as chemotherapeutic agents. Any practical value they may have, however, is often greatly reduced by their ready deamination in vivo by deaminases. Studies have been conducted to determine the relationship between structure and activity for both substrates and inhibitors of adenosine deaminase, some such studies involving ring-opened analogues of nucleosides. To date, however, despite several promising reports of novel compounds, no such compounds have been produced and developed for chemotherapeutic use. The present invention provides certain novel biologically active dinucleotide and nucleoside analogues and processes for their preparation. The nucleoside analogues of the present invention have the general formula: ##STR2## wherein R and R' are independently selected from hydrogen, silyl, substituted silyl, lower alkyl of 1-6 carbon atoms, and phenyl-substituted lower alkyl of 1-6 carbon atoms, and B represents an optionally substituted purine or pyrimidine base selected from the group consisting of adenine, guanine, cytosine, uracil and thymine.
The dinucleotide analogues of the present invention have the general formula: ##STR3## wherein
B and B' represent purine or pyrimidine base compounds independently selected from the group consisting of adenine, cytosine, thymine, guanine and uracil;
each of (X) and (Y) represent methylene groups or (X) and (Y) together represent the group ##STR4## completing a deoxyribose ring;
each of (X') and (Y') represent methylene groups or (X') and (Y') together represent the group ##STR5## completing a deoxyribose ring;
with the proviso that the compound contains not more than one deoxyribose ring;
and R, R' and R" are each independently selected from hydrogen, lower alkyl of 1-6 carbon atoms, phenyl substituted alkyl of 1-6 carbon atoms, halogen substituted alkyl of 1-6 carbon atoms, silyl and substituted silyl.
It will be appreciated that the compounds according to the present invention are closely analogous in structure and groupings to naturally occurring nucleosides and nucleotides. The essential chain arrangements and lengths are maintained. The appropriate O and OH functional groups, which in biological environments actively bind to biological centers, are maintained in their natural sequences and disposition relative to the base, but optionally modified with "protecting" groups. Indeed, the groups adjacent to the bases are so similar in chemical constitution to deoxyribose compounds that they can assume the essential conformation of the deoxyribose ring under appropriate conditions. The fundamental difference is that the compounds of the present invention lack the structural rigidity of carbohydrate ring, which renders them unpredictably different in properties and behaviour. Also, the C-4' position is not chiral, in compounds of formula I, so tht stereoisomers do not arise. Each hydroxyl is primary. There can be no syn-anti isomerism about the glycosidic band.